Defect in the development of thermotolerance and enhanced heat shock protein synthesis in the mouse temperature-sensitive mutant ts85 cells upon moderate hyperthermia

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The effect of exposure to moderate hyperthermia on the induction of thermotolerance and heat shock protein (HSP) synthesis was investigated using mouse FM3A cells and the temperature-sensitive mutant ts85 cells. The thermal sensitivity of the two cell lines was markedly different; the mutant ts85 cells were more sensitive than the parental wild-type FM3A cells to heating at 41 and 44 degrees C. The shift-up treatment of FM3A cells for 3 h at 39.5 degrees C from 33 degrees C induced thermotolerance development to subsequent heating at 44 degrees C, with little if any enhancement of major HSP synthesis. On the other hand, the similar treatment of ts85 cells at the non-permissive temperature of 39.5 degrees C induced significantly enhanced HSP synthesis, but could not induce thermotolerance. The exposure to 41 degrees C also induced thermotolerance in the wild-type cells, but failed to induce tolerance in the mutant ts85 cells. These results suggest that enhanced major-HSP synthesis is neither a sufficient or necessary condition for thermotolerance development upon moderate heat shock. The mechanism of thermotolerance is discussed by relating the observed defect in thermotolerance development to the known defect in ubiquitin-dependent protein degradation system of the mutant ts85 cells at non-permissive temperature.